This invention relates to solid forms of 6-carboxy-2-(3,5-dichlorophenyl)-benzoxazole meglumine (also referred to as “Compound 1”) that are useful in the treatment of transthyretin amyloid diseases, such as senile systemic amyloidosis (SSA), familial amyloid polyneuropathy (FAP) and familial amyloid cardiomyopathy (FAC), in mammals. This invention also relates to compositions including such solid forms, and to methods of using such compositions in the treatment of transthyretin amyloid disease in mammals, especially humans.
Carboxy-2-phenyl-benzoxazoles, such as 6-carboxy-2-(3,5-dichlorophenyl)-benzoxazole, and their salts, are described in U.S. Pat. Nos. 7,214,695 and 7,214,696; and in U.S. Patent Application Publication No. 2010/0120919 (all of which are hereby incorporated by reference in their entireties). Methods of making carboxy-2-phenyl-benzoxazoles, as well as pharmaceutical compositions comprising the same, are also described therein.
Compound 1 stabilizes the protein transthyretin (TTR), dissociation of which is implicated in TTR amyloidosis (i.e., Compound 1 prevents dissociation of the native TTR tetramer into monomers, which results in the inhibition of TTR amyloid fibril formation) and is being developed for use in the treatment of transthyretin amyloid diseases.
Solid forms are of interest to the pharmaceutical industry and especially to those involved in the development of suitable dosage forms. If the solid form is not held constant during clinical or stability studies, the exact dosage form used or studied may not be comparable from one lot to another. It is also desirable to have processes for producing a compound with the selected solid form in high purity when the compound is used in clinical studies or commercial products since impurities present may produce undesired toxicological effects. Certain solid forms may also exhibit enhanced thermodynamic stability or may be more readily manufactured in high purity in large quantities, and thus are more suitable for inclusion in pharmaceutical formulations. Certain solid forms may display other advantageous physical properties such as lack of hygroscopic tendencies, filterability, improved solubility, and enhanced rates of dissolution due to different lattice energies.
The discussion of the background to the invention herein is included to explain the context of the present invention. This is not to be taken as an admission that any of the material referred to was published, known, or part of the common general knowledge in any country as of the priority date of any of the claims.